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Krishnakumar Kizhatil, Haelynn Gim, Graham M. Clark, Simon W John; Sympathetic Innervation of the Developing Aqueous Humor Drainage Structures. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4700. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The nervous system is important in controlling intraocular pressure (IOP) regulation, however the precise mechanisms remain unclear. As a prelude to understanding function of neuronal IOP control, we developed a detailed map of limbal neurons that showed that sympathetic neurons innervate the inner wall of the Schlemm’s canal (SC), which is the last barrier to outflow. To determine when neuronal control of aqueous humor (AQH) outflow begins, we established a developmental time course for limbal sympathetic innervation of the developing SC and vasculature associated with the SC.
We mapped the innervation of the developing SC and associated vasculature in mice at specific postnatal (P) ages from P1.5 to P20 using whole-mounted anterior mouse eye tissue. Blood vessels in the limbal vascular plexus (LVP), SC and the underlying radial blood vessels (RV) were detected by GFP fluorescence in the KDR-GFP mouse strain or using endomucin immunofluorescence. Sympathetic neurons were detected using tyrosine hydroxylase (TH) immunofluorescence and axons were labeled using a neurofilament (NF) antibody. 3D limbal images generated using confocal microscopy. Sympathetic nerves terminating near the SC were identified using Imaris image analysis software.
We saw NF positive axons innervating the vasculature, the LVP and radial vessels, starting at P1.5 mouse eyes. The axon branching in the LVP region grew more complex with age. TH labeling in the LVP and RV axons were present from P1.5. However, innervation of the rudimentary SC between P1.5 and P6, by both NF and TH immunofluorescence, was undetectable. Sympathetic innervation of SC was first detected at P8-P10. Sympathetic termini innervating the developing SC increased in number between the ages of P12-P20.
Our study shows that sympathetic innervation of SC does not begin until late in the development of SC (P8-P10). The SC lumen formation starts at P10 producing a distinct adult like inner and outer wall by P12-P14. Thus, the prominent sympathetic innervation of the SC inner wall starting at P12 could be related to the changes in, or the onset of outflow and its regulation. Given the influence of episcleral venous pressure on IOP, the early and continued sympathetic innervation of the vasculature associated with the SC suggests that the neuronal control of vascular pressure may play a role in AQH drainage.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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